摘要
Background:Systemic lupus erythematosus(SLE)is a particularly heterogeneous autoimmune disease.This study was intended to clarify the correlations between X-inactive-specific transcript(XIST)expression and SLE clinical features and the contribution of XIST to SLE pathogenesis at the transcriptome level.Methods:XIST expression in 79 SLE patients,14 rheumatoid arthritis patients,and 23 healthy controls was determined by quantitative polymerase chain reaction.The Benjamini and Hochberg adjusted method and multivariate linear regression were applied to correct p-values and adjust confounding factors,respectively.Bioinformatic methods were used to explore the function and regulatory mechanism of XIST.Results:XIST was significantly elevated in peripheral blood mononuclear cells and CD4^(+)T cells from SLE patients compared with the levels in healthy controls and had potential diagnostic value for SLE.Notably,XIST expression was positively correlated with the SLE disease activity index and significantly reduced after effective treatment.Moreover,SLE patients with high XIST expression tended to have elevated levels of CD4^(+)T cells,but reduced levels of NK cells.Bioinformatic analyses suggested that XIST may regulate OLFM4 and CEACAM8 expression by acting as a spongy body for miR-20a,miR-92a,miR-106a,and miR-449a.Furthermore,CEACAM8 was significantly upregulated in CD4^(+)T cells from SLE patients and significantly positively correlated with XIST expression.Conclusions:lncRNA XIST,a potential diagnostic and therapeutic biomarker for SLE,is involved in the change of immune cell balance in the peripheral blood of SLE patients.Mechanistically,XIST may regulate the miR-17-92-CEACAM8 axis to achieve this in CD4^(+)T cells.
基金
Natural Science Foundation of Zhejiang Province,Grant/Award Number:LY20H100007
National Natural Science Foundation of China,Grant/Award Number:82071810。